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PubMed1993

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

OBJECTIVE: To compare safety of salmeterol and salbutamol in treating asthma. DESIGN: Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING: General practices throughout the United Kingdom. SUBJECTS: 25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS: Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES: All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS: Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS: Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.

Administration, Inhalation↗
PubMed1995

The prognostic significance of race and survival from breast cancer: a model for assessing the reliability of reported survival differences.

For more than 20 years, black women with breast cancer have been reported to have a lower survival rate than white women with breast cancer. Despite correcting for stage and socioeconomic status, some studies continue to report race-related excess mortality. A reliability scoring system was developed, based primarily on the precision of the staging system used, and the likelihood that the quality of treatment was comparable. Studies that compared the survival of blacks and whites treated for breast cancer from 1968 to 1988 were included in this study. Studies that demonstrated relatively large differences in the 5-year survival between blacks and whites were associated with low reliability scores. Studies that reported little or no difference in 5-year survival rates were associated with relatively high reliability scores. This model and the literature on which it is based suggest that the reported survival differences associated with race can be explained by differences in stage at presentation and by differences in the quality of care received. Efforts directed at early detection and improvements in the quality of care delivered are likely to reduce the excess breast cancer mortality experienced by black women.

Black People↗
PubMed2001

A propensity analysis of cigarette smoking and mortality with consideration of the effects of alcohol.

Although it is well established that cigarette smoking causes excess mortality, the extent of the increased risk has been challenged because self-selection biases and confounding factors may not have been adequately accounted for in prior studies. We therefore performed a propensity analysis on a population-based cohort. A logistic regression model was used to generate a propensity score for current smoking in 6,099 adults (mean age 46 years, 54% men, 36% current smokers) participating in the National Heart Lung and Blood Institute's (NHLBI) Lipid Research Clinic Prevalence Study. During 12 years of follow-up, 513 subjects (8%) died. After adjusting for age, current smoking was strongly associated with death (compared with never and former smokers, relative risk [RR] 2.69, 95% confidence interval [CI] 1.98 to 0.64, p <0.0001 and RR 1.79, 95% CI 1.26 to 2.55, p = 0.001, respectively). After adjusting for a propensity score based on 27 covariates and the covariates themselves, current smoking remained strongly and independently predictive of excessive death risk in smokers compared with never and former smokers (adjusted RR 2.96, 95% CI 2.16 to 4.05, p <0.0001 and adjusted RR 1.87, 95% CI 1.31 to 2.67, p = 0.0006, respectively). Although smokers were more likely to also drink alcohol, an interaction was noted, whereby, after adjustment for propensity score and other covariates, current smoking was associated with a moderately strong increase in mortality among drinkers (adjusted RR 2.00, 95% CI 1.42 to 2.82, p <0.0001), but was also associated with a markedly increased death risk among nondrinkers (adjusted RR 4.74, 95% CI 3.24 to 6.92, p <0.0001). The independent association of smoking with death even after a rigorous propensity analysis argues that it is highly unlikely that the link between smoking and mortality is materially biased or confounded.

Adult↗
PubMed2004

Relationship of early hyperglycemia to mortality in trauma patients.

INTRODUCTION: Recent randomized prospective data suggest that early hyperglycemia is associated with excess mortality in critically ill patients, and tight glucose control leads to improved outcome. This concept has not been carefully examined in trauma patients, and the relationship of early hyperglycemia to mortality from sepsis in this population is unclear. The objective of this study was to determine the relationship different levels of early blood glucose elevation to outcome in a trauma ICU population. METHODS: The records of all patients admitted to the ICU over a 2-year period at a Level I trauma center were reviewed for age, injury severity scores (ISS), admission Glasgow Coma Scale (GCS) score, base deficit (BD), blood glucose, and mortality. Three possible cutoffs in defining hyperglycemia were examined (glucose > or =110 mg/dL, > or =150 mg/dL, > or =200 mg/dL) in relation to infection and mortality. Early hyperglycemia was defined as elevated blood glucose on hospital days 1 or 2. Those with diabetes mellitus were excluded. RESULTS: From 1/00-12/01, 516 eligible patients were admitted to the ICU after injury. Early hyperglycemia occurred in 483 at the > or =110 mg/dL level, 311 at the > or =150 mg/dL level, and 90 patients at the > or =200 mg/dL level. Univariate logistic regression demonstrated a significant relationship between ISS and subsequent infection(p = 0.02) and a trend toward such a relationship in GCS score, glucose > or =150 mg/dL, and glucose > or =200 mg/dL (p = 0.06, 0.12, and 0.06). A similar analysis for the relationship of these variables to eventual mortality showed a significant correlation with all examined variables except glucose > or =110 mg/dL. Multiple logistic regression to control for the effect of age, ISS, GCS score, and BD found early glucose > or =200 mg/dL to be an independent predictor of both infection and mortality while no such relationship was found with > or = 110 mg/dL or > or =150 mg/dL. CONCLUSIONS: Early hyperglycemia as defined by glucose > or =200 mg/dL is associated with significantly higher infection and mortality rates in trauma patients independent of injury characteristics. This was not true at the cutoffs of > or =110 mg/dL or > or =150 mg/dL. These data support the need for a prospective analysis of tight glucose control, keeping serum glucose <200 mg/dL in critically ill trauma patients. However, aggressive maintenance of levels <110 mg/dL as reported by others may not be necessary.

Academic Medical Centers↗
PubMed2003

A simple estimate of mortality attributable to excess weight in the European Union.

OBJECTIVE: To estimate the current burden of mortality attributable to excess weight in the European Union (EU). METHODS: Prevalence of overweight (body mass index, BMI 25-29.9 kg/m(2)) and obesity (BMI >or=30 kg/m(2)) were based on self-reported data from a survey with samples representative of the 15 EU Member States in 1997. Primary source of relative risk (RR) of death by BMI was the first American Cancer Prevention Study (CPS I). Additional calculations were performed to account for effect of smoking (using CPS I data for non- or never-smokers), for pre-existing illness (using the second CPS, CPS II, data for healthy never-smokers) and using RRs derived from European rather than US data (using data from a meta-analysis of prospective studies). Mortality attributable to excess weight was calculated by combining the prevalences of overweight and obesity, the RRs, and the number of deaths in the EU countries. RESULTS: Annual deaths attributable to overweight and obesity totalled approximately 279 000 when RRs for all subjects were used. When RRs for nonsmokers only were applied to the entire population, about 304 000 deaths were attributable to excess weight. In analyses using RRs which controlled for both smoking and history of disease, the number of deaths attributable to excess weight was estimated at about 337 000 based on European data and at about 401 000 based on US data. In the EU, therefore, a minimum of 279 000 deaths were attributable to excess weight (7.7% of all deaths, varying from 5.8% for France through 8.7% for the UK). More attributable deaths occurred among the obese (175 000) than among the overweight (104 000). Around 70% were cardiovascular disease deaths (195 000) and 20% cancer deaths (53 000). CONCLUSION: Mortality attributable to excess weight is a major public health problem in the EU. At least one in 13 annual deaths in the EU are likely to be related to excess weight.

Adult↗
PubMed1987

Educational level and 5-year all-cause mortality in the Hypertension Detection and Follow-up Program. Hypertension Detection and Follow-up Program Cooperative Group.

Excess mortality in persons of lower socioeconomic status is a finding confirmed in many population studies. Among the nearly 11,000 hypertensive trial participants in the population-based Hypertension Detection and Follow-up Program, lower educational level (an indicator of low socioeconomic status) was associated with a 5-year death rate significantly above that found in those with higher education. This report examines whether this excess was observed uniformly within both treatment groups--stepped care and referred care--or whether the more vigorous antihypertensive program of stepped care was able to reduce the mortality gradient associated with education. In addition, impact on mortality of degree of blood pressure control during the trial was assessed within stepped and referred care groups, taking account also of educational level. Finally, the benefit of stepped care compared with referred care (control group) in reducing mortality was analyzed, controlling for education. Referred care participants with less than a high school education had a 5-year death rate twice as high as those with more than a high school education, whereas no such gradient of mortality was seen in the stepped care group. Level of blood pressure control throughout the trial was better in the stepped than in the referred care group and was significantly (inversely) associated with mortality in the stepped care group, regardless of educational level. In the referred care group as well, the better the control of elevated blood pressure (again, regardless of educational level), the lower the mortality, although this inverse association did not quite reach statistical significance in the referred care group.(ABSTRACT TRUNCATED AT 250 WORDS)

Educational Status↗
PubMed1999

British Airways flightdeck mortality study, 1950-1992.

OBJECTIVE: To study the mortality and life expectancy of male British Airways flightdeck crew and to establish whether proportionate mortality excesses shown earlier for brain/CNS cancer, colon cancer and melanoma remained evident. METHODS: A Standardized Mortality Ratio study (SMR) using England and Wales as the comparison population was carried out for 6209 male pilots and 1153 male flight engineers employed for at least 1 yr between January 1, 1950 and December 31, 1992. Internal relative risk comparisons were made between shorthaul and longhaul operations defined broadly as flights within Europe and beyond Europe, respectively. RESULTS: The all-causes SMR for pilots of 61 (592 deaths) and 56 for flight engineers (127 deaths) confirmed the expected Healthy Worker Effect. In pilots apart from the known excess of deaths from aircraft accidents (SMR 14694), most of the comparisons showed significant deficits in mortality. The SMR's for brain/CNS cancer (143) and colon cancer (111) were no longer statistically significant. The SMR of 333 for melanoma was significantly raised in pilots but was not evident in flight engineers. Life expectancy for longhaul pilots and flight engineers was 4-5 yr better than England and Wales for ages 55-65 while the advantage for shorthaul pilots was reduced to between 2-3 yr. Cases of leukemia and aleukaemia in pilots were less than expected and less than the positive excess predicted from modeling based on radiation dose. CONCLUSION: The study confirms that flightdeck crew live longer than the England and Wales population and do not exhibit patterns of death that could be directly attributable to occupation.

Accidents, Aviation↗
PubMed2001

Educational differences in lung cancer mortality in male smokers.

BACKGROUND: To assess the extent of lung cancer mortality differentials by education while adjusting for exposure to tobacco smoke and asbestos based on survey questions. METHODS: Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) Study of 50-69-year-old Finnish male smokers enrolled 1985-1988. These analyses are based on the placebo group and the alpha-tocopherol supplementation group, altogether 14 011 men, with full information on tobacco smoking. Mortality follow-up was to the end of April 1993 and it was based on the complete death certificate register of the Statistics Finland. RESULTS: Lung cancer mortality of basic-educated men was 32% (rate ratio [RR] = 1.32; 95% CI : 0.93-1.87) higher than that of better-educated men in the ATBC Study. The excess is practically unchanged when additional adjustment was made for age at initiation, duration of smoking, current smoking at baseline and at first follow-up, smoke inhalation, occupational exposure to asbestos and interactions between asbestos exposure and all smoking variables. This excess mortality was about 40% of the similar excess observed in the general population of men of similar age. CONCLUSIONS: Educational differences in lung cancer mortality in the total Finnish population are likely to be mainly caused by differences in exposure, particularly to active smoking. Further understanding of the determinants and consequences of socioeconomic differences in smoking behaviour are of major scientific and public health importance.

Aged↗
PubMed1997

Mitral regurgitation: a new clinical perspective.

Mitral regurgitation is a common valvular heart disease, particularly in the elderly population. The timing of surgical repair is controversial, but recent literature suggests a new clinical perspective on the management of this disease. Despite receiving medical treatment and having few initial symptoms, patients with mitral regurgitation due to flail leaflets have an excess mortality rate (6.3% per year) and high morbidity. Ten years after mitral regurgitation has been diagnosed, 90% of the patients have either died or undergone an operation. After surgical correction of mitral regurgitation, left ventricular dysfunction is a frequent complication and is the cause of excess heart failure and mortality. This complication is due to preoperative left ventricular dysfunction but is incompletely predictable with use of current methods. Conversely, considerable progress in surgery has resulted in an extremely low operative mortality rate (about 1% in patients younger than 75 years of age) and high feasibility of valve repair, even in patients with anterior leaflet prolapse. These facts have led to the new perspective that early surgical correction (before occurrence of overt symptoms or left ventricular dysfunction) should be considered when patients are diagnosed with severe mitral regurgitation.

Humans↗
PubMed2005

Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort Study.

BACKGROUND: Little is known about the excess mortality from forms of tobacco use other than cigarette smoking that are widely prevalent in India, such as bidi smoking and the various forms of smokeless tobacco use. We report on absolute and relative risks of mortality among various kinds of ever tobacco users vs never-users in the city of Mumbai, India. METHODS: Using the Mumbai voters' list as the selection frame, 99 570 individuals aged > or = 35 years were interviewed at their homes during 1992-94. At active follow-up (during 1997-99) after 5.5 years, 97 244 (97.7%) were traced. Among these, 7531 deaths (4119 men, 3412 women) were recorded, of which 89% died within study area. It was possible to abstract cause of death information from the records of the municipal corporation for 5470 deaths. These were coded using ICD 10. RESULTS: The adjusted relative risk was 1.37 (95% CI 1.23-1.53) for (men) cigarette smokers and 1.64 (95% CI 1.47-1.81) for bidi smokers, with a significant dose-response relationship for number of bidis or cigarettes smoked. Women were essentially smokeless tobacco users; the adjusted relative risk was 1.25 (95% CI 1.15-1.35). The risk of deaths from respiratory diseases (RR 2.12, 95% CI 1.57-2.87), tuberculosis (RR 2.30, 95% CI 1.68-3.15), and neoplasms (RR 2.60, 95% CI 1.78-3.80) were significantly high in male smokers than never tobacco users. CONCLUSIONS: Bidi is no less hazardous than cigarette smoking, and smokeless tobacco use may also result in significantly increased mortality.

Adult↗
PubMed1985

Air pollution, climate, socioeconomic status and total mortality in the United States.

This study examines the relative effects of air pollution, climate, and socioeconomic status (SES) on total mortality rate for 49 cities in the United States during the period 1968-1970 by using the multivariate regression model. Socioeconomic variables explain a greater percentage of the variation in the total mortality than do air pollution and climate variables. The results showed that excess mortality was associated with concentrations of benzene-soluble organic matter (BSO) and, to a lesser extent, total suspended particulates (TSP). It seemed likely that TSP and BSO were acting as a substitute for one another, without causal relationship. These findings have provided some limited conclusions; and more refined research is proposed.

Age Factors↗
PubMed2003

Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry.

BACKGROUND: Older age has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). As PCI technology evolves and the US population becomes proportionally older, assessment of PCI in older age groups is essential. METHODS: From the National Heart, Lung, and Blood Institute Dynamic Registry, 4620 PCI-treated patients (1997 to 1999) were studied. Differences in clinical presentation, treatment strategy, and inhospital and 1-year outcomes were compared between patient age groups: younger (<65 years, n = 2537); older (65 to 79 years, n = 1776); and elderly (> or =80 years, n = 307). RESULTS: Older and elderly patients had more cardiac and comorbid noncardiac conditions and more extensive and complex arteriosclerosis, including stenoses in bypass grafts. Stent use was similar as age increased (72% vs 73% vs 73%), as was the use of IIb/IIIa receptor antagonists (29% vs 26% vs 28%). Rates of successful treatment of all attempted lesions were 93%, 92%, and 89%, respectively. Adjusted relative risks of inhospital death (1.0 vs 2.91 vs 3.64) and myocardial infarction (1.0 vs 1.35 vs 2.57) increased by age group, as did 1-year mortality rates (1.0 vs 1.87 vs 3.02). However, the relative magnitude of excess mortality rates at 1 year was comparable to that observed by age in the US general population. Age was not associated with 1-year risk of myocardial infarction or coronary artery bypass grafting. CONCLUSIONS: Although new technologies may allow for treatment of complex disease in older and elderly patients with comorbid disease, the increased procedural risk remains substantial in these patients. After PCI, the long-term relative risk of death is similar to that expected among persons of similar ages in the general population.

Age Factors↗
PubMed2002

Acute effects of aldosterone on intracardiac monophasic action potentials.

BACKGROUND: Elevated plasma aldosterone levels represent an independent risk factor for increased mortality in congestive heart failure. Sudden cardiac deaths contribute substantially to the excessive mortality in congestive heart failure and so does atrial fibrillation as one of the major causes of stroke in elderly persons. So far, the electrophysiological properties of aldosterone have not been thoroughly characterized. In the present study, the effects of aldosterone on intracardiac monophasic action potentials were investigated in humans. METHODS AND RESULTS: Monophasic action potentials were recorded in six patients with supraventricular arrhythmias. Eleven ml of 0.9% NaCl (placebo) were injected intravenously, and monophasic action potentials recorded for 10 min. Thereafter, aldosterone (0.5 mg in 0.9% NaCl) was injected and recording of monophasic action potentials continued as previously. The mean action potential duration at 90% repolarization was calculated for the entire 10-min period of each treatment. All patients were in sinus rhythm and had normal electrolyte status. In the placebo period, mean MAPd90 was 287+/-22 ms (mean+/-S.D.), and 299+/-25 ms following aldosterone (P<0.02). After adjustment for heart rate, the difference remained statistically significant (P<0.01). The maximal effect of aldosterone was seen 4-6 min after injection. CONCLUSION: Aldosterone increases monophasic action potential duration within minutes after intravenous application. Therefore, this effect is likely to be mediated nongenomically. It may be hypothesized that aldosterone exerts its unfavorable effects partly via altering myocardial repolarization.

Action Potentials↗
PubMed1998

The incidence of sudden unexpected death in epilepsy (SUDEP) in South Dublin and Wicklow.

Patients with epilepsy have a mortality rate higher than that of the general population. Some of this excess mortality is attributable to sudden unexpected death (SUDEP). We examined the incidence of this phenomenon both retrospectively and prospectively in the population of South Dublin and Wicklow over the period May 1992-1995. Cases were ascertained by examination of post-mortem registers of hospitals serving the area studied. Information on cases was sought from hospital records, general practitioners and families. Fifteen cases (10 male, five female) were identified resulting in an overall incidence rate of SUDEP of 1:680/year for the 3 years of the study. This is the only study of incidence of SUDEP conducted in Ireland and our results are in keeping with incidence rates elsewhere in Europe and the USA.

Adolescent↗
PubMedDate not supplied

Testing the harvesting hypothesis by time-domain regression analysis. I: baseline analysis.

Although the association between air pollution and daily mortality is well established, the mechanisms by which air pollution results in excess mortality are not yet well understood. In particular, there exists debate over whether air pollution has a direct effect on mortality in the general population or simply shortens the life span of frail individuals, a hypothesis referred to as "harvesting." The goal of this investigation is to test the harvesting hypothesis using the time-domain regression method of Dominici et al. (2003a). We conducted simulations based on a two-compartment model that divides the population into a larger group of healthy individuals and a frail subpopulation. Death from air pollution is assumed to take place in two steps, by first moving from healthy population to the frail pool, then death with probability related to the level of air pollution. Using time-domain analysis, we seek to identify data patterns that would be characteristic of harvesting under different scenarios. For a pure harvesting model, time-domain analysis indicates that mortality is associated with a short-term air pollution episode of less than 2 d if the mean residency time in the frail pool is short. If both entrants and deaths depend on the level of air pollution and the rates of entry to and exit from the frail pool are about the same, the log relative risk estimates are essentially unchanged at all time scales. If pollution affects mortality in the frail pool more than entrants, larger effects will occur at shorter time scales.

Air Pollution↗
PubMed2005

Looking back: rheumatoid arthritis--aetiology, occurrence and mortality.

Kellgren and Lawrence performed the first studies of the incidence and prevalence of rheumatoid arthritis (RA) in the UK. These have since been updated in Norfolk. The current annual incidence is 36/100,0000 in women and 14/100,000 in men. The prevalence is 0.8% of the adult population. The incidence, prevalence and mortality of RA have fallen in women in the last 50 yr. Excess mortality is predominantly due to cardiovascular disease. Risk factors for the development of RA include obesity, smoking, high red meat consumption, a previous blood transfusion and an adverse pregnancy outcome. Protective factors include the oral contraceptive pill and adequate fruit intake.

Arthritis, Rheumatoid↗
PubMed1990

Mortality in non-consenters in a post-myocardial infarction trial.

Follow-up of 270 subjects who declined to participate in a trial of oral anticoagulant therapy after acute myocardial infarction revealed a higher mortality (25.6%) than that for participants in the placebo group (20.2%). The excess mortality in terms of odds ratios was 1.35 (90% confidence interval 1.02-1.79). Age was the only predictor of death. The event rate from ischaemic cardiovascular disease was lower among non-consenters than among participants (49.3% vs. 74.8%), as was the rate of death during the first year of follow-up. In conclusion, the differing mortality and dissimilar patterns of specific causes of death in non-consenters and placebo-treated participants emphasize the need for caution in extrapolation of treatment effects to the non-consenting group. Thus the size of the non-consenting group has implications for generalization of the overall results.

Age Factors↗
PubMed1992

Heart failure: to digitalise or not? The view against.

Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.

Angiotensin-Converting Enzyme Inhibitors↗